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透明质酸真皮填充剂的交联参数研究与表征:从设计到产品性能

Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances.

作者信息

Pluda Stefano, Salvagnini Cecilia, Fontana Anna, Marchetti Anna, Di Lucia Alba, Galesso Devis, Guarise Cristian

机构信息

Fidia Farmaceutici S.p.A., via Ponte della Fabbrica 3/A, Abano Terme (PD), 35031 Padova, Italy.

Department of Biology, University of Padova, 35121 Padova, Italy.

出版信息

Gels. 2023 Sep 9;9(9):733. doi: 10.3390/gels9090733.


DOI:10.3390/gels9090733
PMID:37754414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10530960/
Abstract

Despite process similarities, distinctive manufacturing technologies offer hyaluronic acid dermal fillers with different in vitro physicochemical and rheological properties due to peculiar crosslinked hydrogel networks. A better understanding of dermal filler properties could provide specific clinical indications and expectations with more accurate performance correlations. In this study, with an emphasis on the degree of modification, hyaluronic acid concentration and molecular weight, these process parameters were able to modulate dermal filler properties, especially rheology. Moreover, an extensive characterization of commercial hyaluronic acid injectables of the Hyal System line was described to present product properties and help to elucidate related clinical effects. Standardized methodologies were applied to correlate in vitro parameters with feasible clinical indications. In view of an optimized dermal filler design, the results of the extrudability measurements allowed the quantification of the effect of hydrogel composition, rheological properties and needle size on injectability. Composition, dynamic viscosity and needle size showed an impactful influence on hydrogel extrudability. Finally, the positive influence of 200 KDa hyaluronic acid in comparison to fragments of ether-crosslinked hyaluronic acid on fibroblast recognition were shown with a migration assay.

摘要

尽管工艺相似,但由于独特的交联水凝胶网络,不同的制造技术赋予透明质酸真皮填充剂不同的体外物理化学和流变学特性。更好地了解真皮填充剂的特性可以提供更具体的临床适应症,并通过更准确的性能关联得出预期效果。在本研究中,重点关注修饰程度、透明质酸浓度和分子量,这些工艺参数能够调节真皮填充剂的特性,尤其是流变学特性。此外,还对Hyal System系列商用透明质酸注射剂进行了广泛表征,以展示产品特性并有助于阐明相关临床效果。应用标准化方法将体外参数与可行的临床适应症相关联。鉴于优化的真皮填充剂设计,挤出性测量结果能够量化水凝胶组成、流变学特性和针头尺寸对注射性的影响。组成、动态粘度和针头尺寸对水凝胶挤出性有显著影响。最后,通过迁移试验表明,与醚交联透明质酸片段相比,200 kDa透明质酸对成纤维细胞识别具有积极影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/c3b1107f6f60/gels-09-00733-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/70a0a1fe7db0/gels-09-00733-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/a0c8e9e11da0/gels-09-00733-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/fd134135daeb/gels-09-00733-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/f145b64af371/gels-09-00733-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/2b3749c4a3d5/gels-09-00733-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/c3b1107f6f60/gels-09-00733-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/70a0a1fe7db0/gels-09-00733-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/a0c8e9e11da0/gels-09-00733-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/fd134135daeb/gels-09-00733-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/f145b64af371/gels-09-00733-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/2b3749c4a3d5/gels-09-00733-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b67/10530960/c3b1107f6f60/gels-09-00733-g006.jpg

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[6]
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[7]
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本文引用的文献

[1]
Rheological Considerations of Pharmaceutical Formulations: Focus on Viscoelasticity.

Gels. 2023-6-7

[2]
The Rheology and Physicochemical Characteristics of Hyaluronic Acid Fillers: Their Clinical Implications.

Int J Mol Sci. 2022-9-10

[3]
Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods.

Dermatol Ther. 2022-6

[4]
Rheologic and Physicochemical Characteristics of Hyaluronic Acid Fillers: Overview and Relationship to Product Performance.

Facial Plast Surg. 2022-4

[5]
Approach to differentiate between hyaluronic acid skin quality boosters and fillers based on their physicochemical properties.

J Cosmet Dermatol. 2022-1

[6]
Covalently Crosslinked Hydrogels via Step-Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact.

Adv Mater. 2021-6

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Polymers (Basel). 2020-8-11

[8]
Human Histology and Persistence of Various Injectable Filler Substances for Soft Tissue Augmentation.

Aesthetic Plast Surg. 2020-8

[9]
Hyaluronan-based hydrogels via ether-crosslinking: Is HA molecular weight an effective means to tune gel performance?

Int J Biol Macromol. 2019-11-30

[10]
HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study.

J Appl Biomater Funct Mater. 2019

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